Ventricular hypertrophy and presynaptic regulation of sympathetic function

Area of Science:

• Cardiovascular Physiology
• Neuropharmacology

Background:

• Presynaptic muscarinic cholinergic and alpha 2-adrenergic mechanisms modulate sympathetic neural function in normal hearts.
• Regional variations in norepinephrine turnover rate constant (kNE) reflect sympathetic activity.

Purpose of the Study:

• To investigate the role of presynaptic muscarinic and alpha 2-adrenergic mechanisms in cardiac sympathetic regulation in a model of heart hypertrophy.
• To determine if these regulatory mechanisms are altered in the hypertrophied heart of pulmonary artery-constricted guinea pigs.

Main Methods:

• Guinea pigs underwent pulmonary artery constriction or sham operation.
• Animals were pretreated with saline, or a combination of quinuclidinyl benzilate (Q) and yohimbine (Y).
• Norepinephrine turnover rate constant (kNE) was assessed in cardiac regions via radiolabeled tyrosine incorporation under varying temperatures (24°C and 4°C).

Main Results:

• In sham animals, combined Q + Y significantly increased kNE during cold stress, confirming negative feedback.
• Pulmonary artery-constricted animals showed attenuated increases in cardiac kNE compared to sham animals when treated with Q + Y and cold stress.
• These findings indicate altered presynaptic regulation of cardiac sympathetic function in pulmonary artery-constricted guinea pigs.

Conclusions:

• Presynaptic muscarinic cholinergic and alpha 2-adrenergic receptors normally exert negative feedback on cardiac sympathetic neurotransmitter synthesis.
• This regulatory function appears to be impaired in the hypertrophied heart associated with pulmonary artery constriction.
• Alterations in these receptor-mediated mechanisms may contribute to altered cardiac sympathetic function in heart disease.